Study moves in on why astronauts suffer...( A new study by researchers at San Franc...),Health

A new study by researchers at San Francisco VA Medical Center (SFVAMC) moves in on the physiological basis for the bone density loss experienced by people subjected to prolonged periods of bed rest and by astronauts who fly lengthy missions under the weightless conditions of space.

The work, conducted in rats, is an important step toward developing therapies to prevent such bone loss, says senior author Daniel Bikle, MD, co-director of the Special Diagnostic and Treatment Unit at SFVAMC and professor of medicine and dermatology at University of California, San Francisco. Lead author of the study is Takeshi Sakata, who was a postdoctoral fellow in Dr. Bikle's laboratory at the time of the study and is now an orthopedic surgeon at the Kitade Hospital in Gobo, Wakayama, Japan.

The current study builds on animal work Bikle and Sakata published last year, which showed that when bones are relieved of the burden of bearing weight, bone precursor cells fail to respond to insulin-like growth factor one or IGF-I, a biochemical regulator that plays a key role in the proliferation of most cell types. Now Bikle and his team have found that this lack of response occurs because IGF-I does not activate its receptor molecule on the surface of the cells. In addition, the researchers found that the interaction failure is probably triggered by a loss of integrins, proteins found in the membranes of bone cells that enable these cells to sense mechanical changes in their immediate environment. These integrins are also known to regulate the action of growth factors in other cells. The study appears in the March issue of the Journal of Bone and Mineral Research.

"Up until now, researchers have not demonstrated this signaling feedback loop in bone," says Bikle. "But it makes sense: Integrins are mechano-sensors. When the bone is moving and bearing weight, the integrins initiate a signaling process within the cell. This signal, in turn, impacts IGF-I's ability to act
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Contact: Liese Greensfelder
lgreensfelder@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
23-Feb-2004

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